Carbamic acid, N-[[5-[[[2-[2-(dimethylamino)ethoxy]ethoxy]carbonyl]amino]-1,3,3-trimethylcyclohexyl]methyl]-, 2-[2-(dimethylamino)ethoxy]ethyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 Mar - 14 Mar 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Remarks:

incl. certificate for RCC Ltd, Itingen from Swiss Federal Office of Public Health

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

441-100-8

EC Name:

-

Cas Number:

351197-46-1

Molecular formula:

Hill formula: C24 H48 N4 O6 CAS formula: C24 H48 O6 N4

IUPAC Name:

2-[2-(dimethylamino)ethoxy]ethyl N-{[1,3,3-trimethyl-5-(9-methyl-2-oxo-3,6-dioxa-1,9-diazadecan-1-yl)cyclohexyl]methyl}carbamate

Details on test material:

- Name of test material (as cited in study report): UAX-1179
- Physical state / appearance: pale, amber liquid
- Analytical purity: > 99% proprietary tertiary amines
- Lot/batch No.: M. 17-08.01
- Expiration date of the lot/batch: 19-Sep-2003
- Storage condition of test material: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct sunlight, heat and moisture. The sample was stored under dry air (nitrogen).
- Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: 11 weeks (male), 10-11 weeks (females)
- Weight at study initiation: first day of acclimatization (range 1925 - 2000 g); day of treatment (range 2127 - 2332 g)
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ltd, Fullinsdorf) and haysticks for gnawing. Haysticks (QS no. 144101 ) provided by Provimi Kliba AG.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 11 6/01) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12
- Music was played during the daytime light period.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated sites of the same animal served as control.

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: ca. 4 x 4 cm
- Type of wrap if used: This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm tap water: Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of three animals

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Very slight erythema was observed at the test site of all animals 1 hour after removal of the dressing. The test item did not, however, elicit any skin reactions at the application site of any animal at the 24-, 48- or 72- hour readings (all scores 0). The individual mean score for erythema / eschar and oedema for each of the three animals was therefore 0.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining by the test item of the treated skin was observed.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Animal number 62 showed a decrease in body weight during the observation period. The reason for this could not be established due to the short duration of the study. The body weights of all other rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

To evaluate the irritation of the test item (EEC Commission Directive 93121/EEC, April 27, 1993) the mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).

UAX-1179 is considered to be "not irritating" to rabbit skin.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

UAX-1179 is considered to be not irritating.

Executive summary:

The primary skin irritation potential of UAX-1179 was investigated by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits according to OECD TG 404. The test item did not elicit any skin reactions at the application site of any animal at the 24-, 48- and 72-hour readings. Thus, UAX-1179 is considered to be “not irritating” to rabbit skin.